Invasive Micropapillary Component Research Articles

Cytologic features of micropapillary variant urothelial carcinoma in urinary tract cytology: Case series and review of literature.

The micropapillary variant of urothelial carcinoma (MPVUC) is rare and aggressive. Surgical specimens often show atypical micro-clusters (AMCs) of cells with hyperchromatic, pyknotic, peripheral, irregular nuclei with variable nuclear to cytoplasmic ratios. We reviewed urinary tract cytology (UTC) from patients with MPVUC and hypothesized that AMCs would be present similar to those in surgical specimens. The archives were searched from 2000 to 2020 for patients with surgical cases with either MPVUC or conventional high-grade urothelial carcinoma (HGUC) and with prior abnormal UTC. Two pathologists reviewed UTC cases and controls in a blinded manner for AMCs, with quantitation of none, low, moderate, and high. Interrater reliability was compared by quadratic weighted Cohen's Kappa test. The association between numerical average score and MPVUC status was determined by logistic regression. Five patients with invasive MPVUC, one patient with a noninvasive micropapillary component, and 15 control patients with conventional HGUC were included. All patients had prior or concurrent abnormal UTC samples. Increasing category of quantities of AMCs on cytology was associated with micropapillary status (OR 7.9, 95% CI 2.7-118, p= .045), with moderate agreement between raters (Cohen's Kappa 0.54, 95% CI 0.19-0.89, p= .004). In patients with MPVUC on surgical specimen, AMCs were frequently observed on cytology. Similar atypical clusters were observed in patients with nonmicropapillary HGUC, albeit at lower frequency. However, given the WHO recommendation to diagnose micropapillary only if an invasive micropapillary component is present, a specific diagnosis of MPVUC on UTC cannot be based solely on the presence of AMCs.

Clinicopathologic analysis of 10 cases of pulmonary colloid adenocarcinoma and prognostic implication of invasive micropapillary component

BackgroundWe aimed to investigate the clinicopathologic and histopathologic characteristics of colloid adenocarcinoma of the lung. MethodsWe reviewed the data of 10 patients with colloid adenocarcinoma that met the definition and histopathologic criteria of the current classification of the World Health Organization. The clinicopathologic characteristics were analyzed. Comprehensive histologic review and immunohistochemical staining for TTF-1, ALK, CDX2, and MUC5AC as well as a molecular examination for EGFR and KRAS was performed. ResultsAmong 7 men and 3 women (mean age, 69.6 years), three patients had metastasis of the N2 lymph nodes; of these, two experienced recurrence, and one died of the disease. Remaining patients were all alive without metastasis or recurrence of disease. On gross examination, all tumors were circumscribed mucoid masses. Histologically, we observed the characteristic mucin pools that were distending and destroying the alveolar walls and low cellularity of tumor cells. Most tumor cells were tall columnar cells with basally-located bland-looking nuclei and intracytoplasmic mucin. CDX2 and TTF-1 were partially positive in all and four patients, respectively. MUC5AC was positive in all cases, at least focally. Seven cases showed peribronchiolar metaplasia-like, ciliated tumor cells. Three patients with N2 lymph node metastasis showed mild (N = 2) and moderate (N = 1) cytologic atypia in primary tumors. Presence of stromal invasion and/or micropapillary pattern was common findings of cases with N2 lymph metastasis. ConclusionColloid adenocarcinoma is a rare variant of lung adenocarcinoma with distinct clinicopathologic characteristics. The frequently seen ciliated tumor cells may suggest that this tumor might originate from a metaplastic process. Majority had indolent clinical course but presence of stromal invasion or micropapillary pattern may reflect aggressive behavior of colloid adenocarcinoma and may indicate poor prognosis.

Invasive micropapillary component and its clinico-histopathological significance in patients with colorectal cancer.

Micropapillary components are located in distinct, empty spaces resembling lymphatic vessels and consist of clusters of cancer cells that adhere tightly to one another. These structures do not have a fibrovascular core. Invasive micropapillary components (IMPCs) exhibit reverse polarity, which results in a characteristic 'inside-out' structure. The aim of the present study was to examine the histological significance of the micropapillary component in colorectal carcinoma compared with conventional colorectal adenocarcinoma. Among 115 patients, 5 (4.3%) were diagnosed with a micropapillary colorectal component based on hematoxylin and eosin staining and immunohistochemical analysis. To exclude identification of poorly-differentiated clusters of adenocarcinoma cells in the lymphatic vessels, immunohistochemical analysis with D2-40 was performed, and epithelial membrane antigen was used to confirm the specific 'inside-out' structure of IMPCs. IMPCs were observed to positively correlate with histopathological type (P=0.001) and tumor invasion in venous vessels (P=0.033). Furthermore, the presence and number of lymph node metastases was greater in IMPC cases compared with conventional carcinoma cases; however, these differences were not statistically significant (P=0.087 and P=0.094, respectively). In addition, IMPC cases were not significantly associated with the presence of inflammatory infiltrate in the invasive front of the tumor (P=0.098). Therefore, the present study indicates that the IMPC serves a histopathological and prognostic role in the diagnosis of colorectal cancer due to its aggressive and invasive behavior. IMPC is rare in cases of colorectal cancer and remains a great diagnostic challenge in pathomorphology with further detailed investigation required in the future.

Phagocytosis (cannibalism) of apoptotic neutrophils by tumor cells in gastric micropapillary carcinomas.

To identify those with a micropapillary pattern, ascertain relative frequency and document clinicopathological characteristics by reviewing gastric carcinomas. One hundred and fifty-one patients diagnosed with gastric cancer who underwent gastrectomy were retrospectively studied and the presence of a regional invasive micropapillary component was evaluated by light microscopy. All available hematoxylin-eosin (HE)-stained slides were histologically reviewed and 5 tumors were selected as putative micropapillary carcinoma when cancer cell clusters without a vascular core within empty lymphatic-like space comprised at least 5% of the tumor. Tumor tissues from these 5 invasive gastric carcinomas were immunostained using an anti-mucin 1 (MUC1) antibody (clone MA695) to detect the characteristic inside-out pattern and with D2-40 antibody to determine the presence of intratumoral lymph vessels. Detection of intraepithelial neutrophil apoptosis was evaluated in consecutive histological tissue sections by three independent methods, namely light microscopy with HE staining, the conventional terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method and immunohistochemistry for activated caspase-3 (clone C92-605). Among 151 gastric cancers resected for cure, 5 (3.3%) were adenocarcinomas with a micropapillary component. Four of the patients died of disease from 6 to 23 mo and one patient was alive with metastases at 9 mo. All patients had advanced-stage cancer (≥ pT2) and lymph node metastasis. Positive MUC1 immunostaining on the stroma-facing surface (inside-out pattern) of the carcinomatous cluster cells, together with negative immunostaining for D2-40 in the cells limiting lymphatic-like spaces, confirmed the true micropapillary pattern in these gastric neoplasms. In all five cases, several micropapillae were infiltrated by neutrophils. HE staining, TUNEL assay and immunostaining for caspase-3 demonstrated apoptotic neutrophils within cytoplasmic vacuoles of tumor cells. These data suggest phagocytosis (cannibalism) of apoptotic neutrophils by micropapillary tumor cells. Tumor cell cannibalism is usually found in aggressive tumors with anaplastic morphology. Our data extend these observations to gastric micropapillary carcinoma: a tumor histotype analogously characterized by aggressive behavior and poor prognosis. The results are of interest because they raise the intriguing possibility that neutrophil cannibalism by tumor cells may be one of the mechanisms favoring tumor growth in gastric micropapillary carcinomas. This is the first study showing phagocytosis (cannibalism) of apoptotic neutrophils by tumor cells in gastric micropapillary carcinomas.

Five-Year Survival after Surgery for Invasive Micropapillary Carcinoma of the Stomach

Invasive micropapillary carcinoma (IMPC) of the breast, urinary bladder, ovary, and colon has been reported. However, few reports have described IMPC of the stomach. In addition, IMPC has been described as a histological indicator for lymphatic invasion and nodal metastasis, resulting in poor prognosis. We report a case of 5-year survival after surgery for IPMC of the stomach. A 69-year-old woman was admitted to our hospital with symptoms of upper abdominal pain. Upper gastrointestinal endoscopy revealed a tumor at the antrum of the stomach. Histological examination of the biopsy specimen indicated poorly differentiated adenocarcinoma. The patient underwent distal gastrectomy with lymph node dissection. Microscopic examination of the specimen revealed that the tumor consisted of an invasive micropapillary component. Carcinoma cell clusters were floating in the clear spaces. The patient recovered uneventfully and remains alive without recurrence 5 years after surgery.

Stromal micropapillary component as a novel unfavorable prognostic factor of lung adenocarcinoma

BackgroundPulmonary adenocarcinomas with a micropapillary component having small papillary tufts and lacking a central fibrovascular core are thought to result in poor prognosis. However, the component consists of tumor cells often floating within alveolar spaces (aerogenous micropapillary component [AMPC]) rather than invading fibrotic stroma observed in other organs like breast (stromal invasive micropapillary component [SMPC]). We previously observed cases of lung adenocarcinoma with predominant SMPC that was associated with micropapillary growth of tumors in fibrotic stroma observed in other organs. We evaluated the incidence and clinicopathological characteristics of SMPC in lung adenocarcinoma cases.Patients and MethodsWe investigated the clinicopathological characteristics and prognostic significance of SMPC in lung adenocarcinoma cases by reviewing 559 patients who had undergone surgical resection. We examined the SMPC by performing immunohistochemical analysis with 17 antibodies and by genetic analysis with epidermal growth factor receptor (EGFR) and KRAS mutations.ResultsSMPC-positive (SMPC(+)) tumors were observed in 19 cases (3.4%). The presence of SMPC was significantly associated with tumor size, advanced-stage disease, lymph node metastasis, pleural invasion, lymphatic invasion, and vascular invasion. Patients with SMPC(+) tumors had significantly poorer outcomes than those with SMPC-negative tumors. Multivariate analysis revealed that SMPC was a significant independent prognostic factor of lung adenocarcinoma, especially for disease-free survival of pathological stage I patients (p = 0.035). SMPC showed significantly higher expression of E-cadherin and lower expression of CD44 than the corresponding expression levels shown by AMPC and showed lower surfactant apoprotein A and phospho-c-Met expression level than corresponding expression levels shown by tumor cell components without a micropapillary component. Fourteen cases with SMPC(+) tumors (74%) showed EGFR mutations, and none of them showed KRAS mutations.ConclusionsSMPC(+) tumors are rare, but they may be associated with a poor prognosis and have different phenotypic and genotypic characteristics from those of AMPC(+) tumors.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9433341526290040.

Clinicopathological features of stomach cancer with invasive micropapillary component

Invasive micropapillary carcinoma has been recognized as a rare disease entity with aggressive tumor behavior. However, few reports have described invasive micropapillary carcinoma in the gastrointestinal tract, particularly its involvement in gastric cancer. We retrospectively analyzed 930 patients diagnosed with gastric cancer who underwent gastrectomy, and we then histopathologically evaluated the existence of a regional invasive micropapillary component. Clinicopathological features were investigated in patients with an invasive micropapillary component and compared with such features in 100 patients with gastric adenocarcinoma, selected as stage-matched controls, who underwent gastrectomy during the same period. Of the 930 patients, 14 were histopathologically diagnosed with gastric cancer with a regional invasive micropapillary component. There were no significant differences in age, gender, tumor location, macroscopic type, or type of surgery between patients with an invasive micropapillary component and the pT-matched controls. Histopathologically, significant differences were observed in lymphatic infiltration, venous invasion, the percentage of cases with lymph node metastasis, and the median number of metastatic lymph nodes. The three-year disease-free and overall survival rates of patients with an invasive micropapillary component were 40.5 and 59.3%, respectively, compared with those for the stage-matched controls, which were 72.6 and 80.6%, respectively (p=0.02 and 0.07). Patients with gastric cancer with a regional invasive micropapillary component showed marked cancer infiltration in the lymphatic pathway and poor prognosis after gastrectomy.

A case of HER-2-positive advanced inflammatory breast cancer with invasive micropapillary component showing a clinically complete response to concurrent trastuzumab and paclitaxel treatment

We report a case of HER-2-positive advanced inflammatory breast cancer with invasive micropapillary component showing a complete response to trastuzumab and paclitaxel treatment. A 37-year-old woman was referred to our hospital for right breast swelling with broad skin redness and right axillary tumor. Ipsilateral infraclavicular and contralateral axillary lymph nodes swelling were also recognized. The histopathological findings of core-needle biopsy specimens from primary breast tumor and ipsilateral axillary lymph node were invasive ductal carcinoma with a micropapillary component. Immunohistochemical examination gave a negative result for estrogen receptor (ER)/progesterone receptor (PgR), and overexpression of HER-2 (Hercep Test 3+). Advanced inflammatory breast cancer with an invasive micropapillary component was diagnosed (T4d N3 M1 (LYM), stage IV). The patient was treated with combination chemotherapy using weekly paclitaxel and trastuzumab. After administration of three courses, the breast swelling, skin redness, and lymph node swelling disappeared completely. She maintained complete remission of disease for 12 months and was judged to have a clinically complete response by the RECIST criteria. Invasive micropapillary carcinoma is known to be an aggressive histological type associated with a high incidence of lymph node metastasis and poor prognosis. This is the first reported case of advanced inflammatory breast cancer with an invasive micropapillary component showing a clinically complete response to trastuzumab-containing treatment. This report suggests trastuzumab-containing chemotherapy is a promising therapy for HER-2-positive advanced invasive micropapillary carcinoma.

Pleural malignant mesothelioma with invasive micropapillary component and its association with pulmonary metastasis

The micropapillary pattern (characterized by papillary structure with tufts lacking a central fibrovascular core) is a predictor of aggressive carcinoma. The purpose of the present study was to review 34 pleural malignant mesotheliomas (21 epithelioid, five sarcomatoid, seven biphasic and one lymphohistiocytoid), with special reference to the presence of invasive micropapillary component. Two invasive micropapillary pattern-positive tumors were identified. The invasive micropapillary pattern was seen to have a focal distribution in 15-20% of the tumor tissues. The majority of the invasive micropapillary clusters expressed MUC1 along the outer cell surface. Analysis of pleural malignant mesotheliomas with epithelioid features and with or without invasive micropapillary pattern (21 epithelioid and seven biphasic subtypes) indicated pulmonary micrometastases in only the invasive micropapillary-positive tumors (P < 0.015), and the spread was probably via the lymphatics. Lymphatic involvement (confirmed on immunohistochemistry with D2-40 antibody) and lymph node metastasis were found in both of the invasive micropapillary-positive tumor patients, whereas they were noted in only one of 10 (10%, P < 0.046) and three of nine (30%) invasive micropapillary-negative patients. To the authors' knowledge this is the first study to indicate the presence of invasive micropapillary component in pleural malignant mesothelioma. This component can predict more aggressive lymphatic spread, similar to that of carcinomas in other organs with micropapillary pattern.

Luminal group may give more benefit for invasive micropapillary carcinoma component breast cancer patients: experience from Cancer Hospital Fudan University.

Abstract Abstract #6152 Objective: Comparative studies on clinical features and outcomes of very rare invasive micropapillary carcinoma of breast cancer of 4 subtypes by immunohistochemistry staining.&amp;#x2028; Methods: From Aug 2005 to Mar 2008, a total of 52 breast cancer patients(BCPs) with an invasive micropapillary component (IMPC) among 1951 Chinese BCPs with complete of clinicopathologic data in our institution were enrolled into a retrospective analysis. We characterized all these 52 patients and analyzed using various parameters.&amp;#x2028; Results: The 52 cases of breast carcinoma with an IMPC all occurred in women. Mean age was 51 years (range from 26-82). All of these patients had breast masses; one also had metastasis to the supraclavicular lymph node at the time of diagnosis., mean tumor size was 2.83cm(T2), 23.08%(12/52) was pure invasive micropapillary carcinoma, and lymph node positive percentage was 75.59 %( 36/51).Fifty one patients received surgery, while one of them lost the chance of surgery. Forty of them received the modified mastectomy while one was performed lumpectomy due to old age. One was performed LAND alone and four were performed lumpectomy and sentinel lymph node biopsy.&amp;#x2028; By using IHC staining, when we regard HER2/neu 0 and +as negative. The Luminal A group, Luminal B, trip-negative, HER2+ /ER- were 76.92% (40/52), 11.54 %( 6/52), 7.69 %( 4/52), 3.85 %( 2/52), respectively. Compared to the database of 2005 breast cancer carcinoma in our institution, there was more Luminal A group patients than the whole group (P=0.01, chi-square test.), more Luminal B (P=0.028, Fisher exact possibility test), less trip-negative group (P=0.001, chi-square test). The positive lymph node among the Luminal A group, Luminal B, trip-negative, HER2+ /ER- were 65%,80%, 100%, 100%, respectively, while the lymphvascular invasion were 55%,33.33%,50%,50%,respectively, Mulifocality in Luminal A was 25% , 16.67% in Luminal B , while 50% in both trip-negative and HER2+/ER-.&amp;#x2028; Twenty-one of them received both anthracyclines and Taxane, while 27 only received anthracyclines, Four patients only were received only AIs due to old age. All the luminal group patients received endrocine therapy after chemo. After nearly 14 months (2∼34 months) follow up, thirty-six women were disease free, one had local recurrence, and 1 had lung metastasis, while 1 had ovary carcinoma when the diagnosis of breast malignant, one patient lost following up due to mental disorder. Among the luminal B, one had metastasis when diagnosis, others were disease free. One woman of the trip-negative died of non-breast cancer disease,the HER2+/ER- group was no recurrence or metastasis.&amp;#x2028; Discussion: The prelimary results showed that more luminal group in the IMPC may get benefit from the endocrine therapy. However the number of these cases is small and follow-up time is not very long, further studies are necessary to explain these rare and unique pattern of invasive carcinoma. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6152.

Aggressive invasive micropapillary salivary duct carcinoma of the parotid gland

The presence of invasive micropapillary component has been reported to be associated with salivary duct carcinoma and poor outcomes. Herein is described a rare case of invasive micropapillary salivary duct carcinoma of the parotid gland in a 60-year-old man. The micropapillary component was approximately 70% of the area of the tumor. Squamous differentiation was focally seen adjacent to the micropapillary component. On immunohistochemistry the ordinary salivary duct carcinoma component was positive for gross cystic disease fluid protein-15 (GCDFP-15), androgen receptor (AR), and HER2/neu, whereas both micropapillary and squamous components were negative for GCDFP-15 and AR. Immunohistochemical staining for D2-40 highlighted the lymph vessel invasion of tumor cells. This patient developed metastases in the lymph nodes of the neck, and also in the liver, lung, and brain. The lymph nodes and liver metastases had both ordinary salivary duct carcinoma and micropapillary components. The patient died of tumor 11 months after the initial surgical operation. The results support that the presence of micropapillary component is associated with more aggressive behavior of salivary duct carcinoma. It is also important for pathologists to recognize that GCDFP-15 and AR expression can be reduced in micropapillary carcinoma in the differential diagnosis of metastatic tumor.

Gastric Remnant Adenocarcinoma with Micropapillary Component

An invasive micropapillary carcinoma (IMPC) is defined as a carcinoma composed of small clusters of tumor cells lying within clear spaces simulating vascular channels [1]. It is a histological variant of invasive breast carcinoma with poor clinical prognosis [2, 3]. This distinct histological pattern has been described in various organs, including the urinary bladder, lung, ovary, and major salivary glands [4-8]. Although rarely observed as a pure histological component, IMPC is usually mixed with otherwise conventional carcinoma [3] and is therefore often referred to as carcinoma with a micropapillary component. In cases of adenocarcinoma with a micropapillary component, an abrupt transition is usually seen between the invasive micropapillary component and conventional adenocarcinoma [3]. IMPCs are all invariably associated with high aggressiveness, extensive lymphovascular invasion, extensive lymph node metastases, and poor prognosis [1-3]. We describe the first case of primary IMPC originating in the stomach as a histologic subcomponent of recurrent gastric adenocarcinoma.

Invasive micropapillary salivary duct carcinoma: a distinct histologic variant with biologic significance.

An invasive micropapillary component has been described in tumors of several organs and is nearly always associated with aggressive biologic behavior. We present 14 cases of salivary duct carcinoma (SDC) with an invasive micropapillary component (invasive micropapillary SDC) and compare the clinicopathologic findings of these cases with those of cases of conventional SDC. The mean age of the 14 patients (10 men, 4 women) was 65.8 years (range, 26-80 years). The mean size of the tumors was 2.4 cm (range, 1.3-5 cm). The parotid gland was involved in 12 patients and the submandibular gland in 2. Histologically, all tumors had an invasive micropapillary architecture admixed with features typical for SDC. Invasive micropapillary carcinoma was characterized by morula-like small cell clusters without fibrovascular cores, surrounded by a clear space. Tumor cells exhibited moderate- to high-grade nuclear features, conspicuous nucleoli, and eosinophilic cytoplasm. This component was distributed diffusely in 9 tumors and focally in 5. Angiolymphatic and perineural invasion was seen in all tumors. A residual pleomorphic adenoma was detected in four tumors. Of the 12 tumors examined, all were diffusely positive for cytokeratin 7 and epithelial membrane antigen (with a distinctive "inside-out" pattern) but negative for cytokeratin 20. Tumors were frequently immunoreactive for BRST-2 (gross cystic disease fluid protein-15) and androgen receptor protein. Aberrant expression of HER-2/neu or p53 was detected in seven tumors each. The mean Ki-67 labeling index was 33.1% (range, 6.3%-61.6%). All 14 patients with invasive micropapillary SDC had cervical or periglandular lymph node metastasis, and this value was significantly higher than for conventional SDCs. Local recurrence developed in 4 patients and distant metastatic disease in 9. Clinical follow-up (mean, 25.5 months) was available for 13 patients: 9 died of disease within 24 months after the diagnosis (mean, 17.6 months), 1 was alive with metastatic disease at 19 months, and 3 were free of disease. Overall survival of these patients with invasive micropapillary SDC was significantly shorter than that of patients with conventional SDC (n = 49) in our series (P = 0.031). Our results suggest that invasive micropapillary SDC is a distinct, aggressive variant of SDC, with a propensity for extensive lymph node metastasis and rapid disease progression.

Invasive micropapillary carcinoma of the breast: Eighty cases of an underrecognized entity

Eighty cases of infiltrating duct carcinoma of the breast with a pure or partial micropapillary component are reported. The cases were analyzed using various parameters, including age at presentation, tumor size, tumor grade, presence of lymphatic invasion, and axillary lymph node status. The patients' age at presentation ranged from 36 to 92 years (mean, 58.8 years). Tumor size ranged from 0.1 to 10 cm (mean, 2.0 cm); 67.5% (54 of 80) were poorly differentiated, and 32.5% (26 of 80) were moderately differentiated; 62.5% (50 of 80) of the cases had lymphatic invasion; 72.3% (47 of 65) of cases with axillary dissections had positive lymph nodes; and 25% (20 of 80) of the tumors were ≤1.0 cm and 7.5% (6 of 80) were ≤0.5 cm. The characteristics of these small tumors with an invasive micropapillary component have not previously been reported. Despite their minute size, these small micropapillary carcinomas seem to show the same proclivity for lymphatic spread and nodal dissemination as larger tumors with this unique histologic pattern. HUM PATHOL 32:583-589. Copyright © 2001 by W.B. Saunders Company